This proposal describes experiments investigating the interactions between Dirofilaria immitis, the nematode agent of dog heartworm, and various potential mosquito vector species. Previous studies, including our own, have shown that mosquito species display diverse response to D. immitis infection. We are examining these responses in refractory and susceptible strains of Aedes taeniorhynchus (an excellent vector) and in Anopheles quadrimaculatus a poor vector). Dirofilaria larvae spend the first three larval stages in the Malpighian tubules of the mosquito. We are studying cellular and subcellular interactions between D. immitis and the Malpighian tubule cells. The effects of D. immitis infection on vector survival and reproductive capacity will be investigated in all three mosquito species. We will examine the enzyme pathways associated with intracellular melanization of the parasites in the Malpighian tubules. In the refractory strain of Aedes aegypti, D. immitis prelarvae fail to develop normally. We are examining the hypothesis that this block in development is due to an antiblastic factor present in the cells of the Malpighian tubule. Techniques to be employed include gel electrophoretic analysis of tissues from refractory and susceptible strains of A. aegypti and tissue culture of mosquito Malpighian tubule cells. The ultrastructure of developmentally-blocked prelarvae will be examined as well. These studies are intended to provide a physiological explanation at the cellular level for the extreme variabilities observed in the vector capacities of mosquito species with regard to D. immitis and other nematodes.